{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T04:36:57Z","timestamp":1792557417157,"version":"4.5.0"},"reference-count":32,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5538","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2001,9,21]]},"abstract":"<jats:p>The molecular adapter Fyb\/Slap regulates signaling downstream of the T cell receptor (TCR), but whether it plays a positive or negative role is controversial. We demonstrate that Fyb\/Slap-deficient T cells exhibit defective proliferation and cytokine production in response to TCR stimulation. Fyb\/Slap is also required in vivo for T cell\u2013dependent immune responses. Functionally, Fyb\/Slap has no apparent role in the activation of known TCR signaling pathways, F-actin polymerization, or TCR clustering. Rather, Fyb\/Slap regulates TCR-induced integrin clustering and adhesion. Thus, Fyb\/Slap is the first molecular adapter to be identified that couples TCR stimulation to the avidity modulation of integrins governing T cell adhesion.<\/jats:p>","DOI":"10.1126\/science.1063397","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T05:39:52Z","timestamp":1027748392000},"page":"2260-2263","source":"Crossref","is-referenced-by-count":234,"title":["Positive Regulation of T Cell Activation and Integrin Adhesion by the Adapter Fyb\/Slap"],"prefix":"10.1126","volume":"293","author":[{"given":"Emily K.","family":"Griffiths","sequence":"first","affiliation":[{"name":"Amgen Institute, 620 University Avenue, Toronto, Ontario, Canada M5G 2C1."},{"name":"Ontario Cancer Institute, University Health Network, and Departments of Medical Biophysics and Immunology, University of Toronto, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Connie","family":"Krawczyk","sequence":"additional","affiliation":[{"name":"Amgen Institute, 620 University Avenue, Toronto, Ontario, Canada M5G 2C1."},{"name":"Ontario Cancer Institute, University Health Network, and Departments of Medical Biophysics and Immunology, University of Toronto, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young-Yun","family":"Kong","sequence":"additional","affiliation":[{"name":"Amgen Institute, 620 University Avenue, Toronto, Ontario, Canada M5G 2C1."},{"name":"Ontario Cancer Institute, University Health Network, and Departments of Medical Biophysics and Immunology, University of Toronto, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Raab","sequence":"additional","affiliation":[{"name":"Division of Tumor Immunology, Dana-Farber Cancer Institute, and Departments of Pathology and Medicine, Harvard Medical School, Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon J.","family":"Hyduk","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto General Hospital Research Institute, Toronto, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denis","family":"Bouchard","sequence":"additional","affiliation":[{"name":"Amgen Institute, 620 University Avenue, Toronto, Ontario, Canada M5G 2C1."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera S.","family":"Chan","sequence":"additional","affiliation":[{"name":"Ontario Cancer Institute, University Health Network, and Departments of Medical Biophysics and Immunology, University of Toronto, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivona","family":"Kozieradzki","sequence":"additional","affiliation":[{"name":"Amgen Institute, 620 University Avenue, Toronto, Ontario, Canada M5G 2C1."},{"name":"Ontario Cancer Institute, University Health Network, and Departments of Medical Biophysics and Immunology, University of Toronto, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio J.","family":"Oliveira-dos-Santos","sequence":"additional","affiliation":[{"name":"Amgen Institute, 620 University Avenue, Toronto, Ontario, Canada M5G 2C1."},{"name":"Ontario Cancer Institute, University Health Network, and Departments of Medical Biophysics and Immunology, University of Toronto, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Wakeham","sequence":"additional","affiliation":[{"name":"Amgen Institute, 620 University Avenue, Toronto, Ontario, Canada M5G 2C1."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela S.","family":"Ohashi","sequence":"additional","affiliation":[{"name":"Ontario Cancer Institute, University Health Network, and Departments of Medical Biophysics and Immunology, University of Toronto, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myron I.","family":"Cybulsky","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto General Hospital Research Institute, Toronto, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher E.","family":"Rudd","sequence":"additional","affiliation":[{"name":"Division of Tumor Immunology, Dana-Farber Cancer Institute, and Departments of Pathology and Medicine, Harvard Medical School, Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josef M.","family":"Penninger","sequence":"additional","affiliation":[{"name":"Amgen Institute, 620 University Avenue, Toronto, Ontario, Canada M5G 2C1."},{"name":"Ontario Cancer Institute, University Health Network, and Departments of Medical Biophysics and Immunology, University of Toronto, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/S1074-7613(00)80315-5","volume":"5","author":"Wange R. L.","year":"1996","unstructured":"Wange R. L., Samelson L. E., Immunity 5, 197 (1996).","journal-title":"Immunity"},{"key":"e_1_3_1_3_2","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/S0092-8674(00)80953-8","volume":"96","author":"Rudd C. E.","year":"1999","unstructured":"Rudd C. E., Cell 96, 5 (1999).","journal-title":"Cell"},{"key":"e_1_3_1_4_2","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1146\/annurev.immunol.17.1.89","volume":"17","author":"Clements J. L.","year":"1999","unstructured":"Clements J. L., Boerth N. J., Lee J. R., Koretzky G. A., Annu. Rev. Immunol. 17, 89 (1999).","journal-title":"Annu. Rev. Immunol."},{"key":"e_1_3_1_5_2","doi-asserted-by":"crossref","first-page":"7493","DOI":"10.1073\/pnas.94.14.7493","volume":"94","author":"da Silva A. J.","year":"1997","unstructured":"da Silva A. J., et al., Proc. Natl. Acad. Sci. U.S.A. 94, 7493 (1997).","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"e_1_3_1_6_2","doi-asserted-by":"crossref","first-page":"11674","DOI":"10.1074\/jbc.272.18.11674","volume":"272","author":"Musci M. A.","year":"1997","unstructured":"Musci M. A., et al., J. Biol. Chem. 272, 11674 (1997).","journal-title":"J. Biol. Chem."},{"key":"e_1_3_1_7_2","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1083\/jcb.149.1.181","volume":"149","author":"Krause M.","year":"2000","unstructured":"Krause M., et al., J. Cell Biol. 149, 181 (2000).","journal-title":"J. Cell Biol."},{"key":"e_1_3_1_8_2","doi-asserted-by":"crossref","first-page":"28427","DOI":"10.1074\/jbc.274.40.28427","volume":"274","author":"Veale M.","year":"1999","unstructured":"Veale M., et al., J. Biol. Chem. 274, 28427 (1999).","journal-title":"J. Biol. Chem."},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.281.5375.416"},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81422-1"},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.281.5375.413"},{"key":"e_1_3_1_12_2","doi-asserted-by":"crossref","first-page":"21170","DOI":"10.1074\/jbc.274.30.21170","volume":"274","author":"Raab M.","year":"1999","unstructured":"Raab M., Kang H., da Silva A., Zhu X., Rudd C. E., J. Biol. Chem. 274, 21170 (1999).","journal-title":"J. Biol. Chem."},{"key":"e_1_3_1_13_2","doi-asserted-by":"crossref","first-page":"5143","DOI":"10.1074\/jbc.275.7.5143","volume":"275","author":"Boerth N. J.","year":"2000","unstructured":"Boerth N. J., Judd B. A., Koretzky G. A., J. Biol. Chem. 275, 5143 (2000).","journal-title":"J. Biol. Chem."},{"key":"e_1_3_1_14_2","unstructured":"Web fig. 1 Web table 1 and supplementary Web text describing the gene-targeting strategy and T and B cell phenotypes are available at Science Online at www.sciencemag.org\/cgi\/content\/full\/293\/5538\/2260\/DC1."},{"key":"e_1_3_1_15_2","unstructured":"Lymph node T cells were purified using magnetic beads (Dynal Oslo Norway) and analyses of proliferation cytokine production calcium flux biochemistry and clustering were performed as described (28)."},{"key":"e_1_3_1_16_2","unstructured":"Immunizations and measurements of antibody production were performed as described (29). Enzyme-linked immunosorbent assay (ELISA) analysis showed that basal levels of IgM IgG1 IgG2a IgG2b IgG3 IgA and IgE were similar in fyb\/slap \u2212\/\u2212 and fyb\/slap +\/\u2212 chimeric mice."},{"key":"e_1_3_1_17_2","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1016\/S0092-8674(00)80879-X","volume":"101","author":"Machesky L. M.","year":"2000","unstructured":"Machesky L. M., Cell 101, 685 (2000).","journal-title":"Cell"},{"key":"e_1_3_1_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80884-3"},{"key":"e_1_3_1_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81559-7"},{"key":"e_1_3_1_20_2","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1016\/S0960-9822(98)70224-6","volume":"8","author":"Fischer K. D.","year":"1998","unstructured":"Fischer K. D., et al., Curr. Biol. 8, 554 (1998).","journal-title":"Curr. Biol."},{"key":"e_1_3_1_21_2","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1016\/S0955-0674(00)00129-0","volume":"12","author":"van Kooyk Y.","year":"2000","unstructured":"van Kooyk Y., Figdor C. G., Curr. Opin. Cell. Biol. 12, 542 (2000).","journal-title":"Curr. Opin. Cell. Biol."},{"key":"e_1_3_1_22_2","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/S0065-2776(08)60024-3","volume":"72","author":"Shimizu Y.","year":"1999","unstructured":"Shimizu Y., Rose D. M., Ginsberg M. H., Adv. Immunol. 72, 325 (1999).","journal-title":"Adv. Immunol."},{"key":"e_1_3_1_23_2","unstructured":"G. A. van Seventer"},{"key":"e_1_3_1_23_3","doi-asserted-by":"crossref","first-page":"4579","DOI":"10.4049\/jimmunol.144.12.4579","volume":"144","author":"Shimuzu Y.","year":"1990","unstructured":"Shimuzu Y., Horgan K. J., Shaw S., J. Immunol. 144, 4579 (1990).","journal-title":"J. Immunol."},{"key":"e_1_3_1_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/341619a0"},{"key":"e_1_3_1_25_2","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/S0955-0674(97)80127-5","volume":"9","author":"Kolanus W.","year":"1997","unstructured":"Kolanus W., Seed B., Curr. Opin. Cell Biol. 9, 725 (1997).","journal-title":"Curr. Opin. Cell Biol."},{"key":"e_1_3_1_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)00120-3"},{"key":"e_1_3_1_27_2","unstructured":"T cells in 2.5% bovine serum albumin (BSA) in phosphate-buffered saline (PBS) were added to plates coated with fibronectin BSA or recombinant mlCAM-1 (gift of J. Collard The Netherlands Cancer Institute) and allowed to settle with treatment [medium alone anti-CD3 (2 \u03bcg\/ml) or PMA (100 ng\/ml)] for 1 hour at 4\u00b0C. Samples were incubated at 37\u00b0C for 12 min followed by washing with 2.5% BSA in PBS. Adherent cells were released with 10 mM EDTA in calcium-and-magnesium-free PBS and were counted by trypan blue exclusion. Studies addressing adhesion under shear stress were performed as described (30)."},{"key":"e_1_3_1_28_2","unstructured":"L. Geng S. Pfister S.-K. Kraeft C. E. Rudd Proc. Natl. Acad. Sci. U.S.A. in press."},{"key":"e_1_3_1_29_2","doi-asserted-by":"crossref","unstructured":"C. Krawczyk et al. Immunity 13 463 (2000).","DOI":"10.1016\/S1074-7613(00)00046-7"},{"key":"e_1_3_1_30_2","unstructured":"M. F. Bachmann et al. J. Immunol. 163 137 (1999)."},{"key":"e_1_3_1_31_2","doi-asserted-by":"crossref","first-page":"746","DOI":"10.4049\/jimmunol.164.2.746","volume":"164","author":"Chan J. R.","year":"2000","unstructured":"Chan J. R., Hyduk S. J., Cybulsky M. I., J. Immunol. 164, 746 (2000).","journal-title":"J. Immunol."},{"key":"e_1_3_1_32_2","unstructured":"We thank E. Rubin T. Wada T. Sasaki J. Irie-Sasaki A. Shahinian M. Crackower N. Joza K. Bachmaier and R. Sarao for comments and assistance and M. Saunders for scientific editing. We thank J. Collard and G. Koretzky for reagents. E.K.G. is supported by a scholarship from the Natural Sciences and Engineering Research Council (NSERC) of Canada. C.E.R. is a Principal Research Fellow of the Wellcome Trust London. J.M.P. is supported by Amgen grants from the Canadian Institutes for Health Research (CIHR) the National Cancer Institute of Canada (NCIC) the Premier's Research Excellence Award (PREA) and the Canadian Network for Vaccines and Immunotherapeutics of Cancer and Chronic Viral Disease (CANVAC). J.M.P. holds a Canadian Research Chair in Cell Biology."}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.1063397","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T16:55:43Z","timestamp":1704819343000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.1063397"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,9,21]]},"references-count":32,"journal-issue":{"issue":"5538","published-print":{"date-parts":[[2001,9,21]]}},"alternative-id":["10.1126\/science.1063397"],"URL":"https:\/\/doi.org\/10.1126\/science.1063397","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1001925.31108","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.1001925.29255","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.1001925.11654","asserted-by":"object"}]},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,9,21]]}}}